Kinetic analysis of plasma VLDL-TG and VLDL-remnant-TG turnover in anesthetized rats

We have estimated the turnover and relative pool sizes of nascent-VLDL-TG and VLDL-remnants-TG in anesthetized rats. [1-¹⁴C]Palmitoyl- and [2-³H]glyceryl-labeled “VLDL”-TG (including nascent VLDL-TG and VLDL-remnants-TG) were prepared by injecting labeled palmitate and glycerol into donor rats. Labeled serum from these rats was then injected intravenously into nembutalized male rats and serial blood samples taken for 30 min. Special care was taken to define any early components in the labeled “VLDL”-TG disappearance curves. In other experiments, the donors were rendered functionally hepatectomized 30 min after injection of³H-glycerol and the endogenous labeled VLDL-TG was allowed to circulate 30–60 min before collection of the TG-labeled VLDL-remnants-containing serum. The latter was injected into 4 recipient nembutalized rats and the remnant-TG-turnover measured by serial sampling as above. In two cases,¹⁴C-“VLDL” and³H-VLDL-remnants were injected as a single bolus into ether-anesthetized rats. Despite its complex composition, “VLDL”-TG in most cases disappeared in a single exponential fashion for 30 min with an average half-life of 5.9 min in nembutalized and 2.8 in ether-anesthetized rats. VLDL-remnants-TG showed a more complex behavior, but contained a major rapid component with a mean t_1/2 of ca. 1.5 min in both groups. The data, analyzed by multicompartmental analysis, were fitted to a simple model in which turnover of a larger nascent VLDL-TG pool with formation of a more rapidly turning over smaller pool of VLDL-remnant-TG is the rate-limiting step in overall TG removal from the d<1.006 fraction of rat serum. The data are consistent with our theoretical prediction that under these conditions the kinetics of the VLDL-remnants cannot be resolved from analysis of the total composite “VLDL” (nascent plus remnant) pool.     

Radiology in primary hyperaldosteronism

Autonomous hypersecretion of aldosterone (primary hyperaldosteronism) is caused by either hyperplasia (usually bilateral) or an adenoma (frequently unilateral) of the adrenal cortex. Systemic hypertension due to an aldosteronoma is a potentially curable condition through surgical extirpation of the offending organ. In our experience with 37 patients clinically suspected to have primary hyperaldosteronism, radiological methods contributed significantly in preoperative diagnosis. These included (1) selective bilateral adrenal vein catheterization and blood sample collection, (2) adrenal venography, and (3) radioisotope adrenal scan. Unilateral hyperfunction could be accurately detected by the aldosterone assays from the collected samples. When adrenal venography was technically satisfactory, a nodule or aggregate of nodules measuring at least 7 mm and located on the margin of the gland or 1.5 cm or more in diameter when located in the center of the gland were readily identified. Enlarged adrenal gland on venography, in itself, was not a dependable index of a hyperfunctioning gland. Presence of a higher uptake on one side on the radioisotope adrenal scan did not always indicate the hyperfunctioning gland, but lack of lateralization of adrenal hyperfunction was more accurately predicted on the radioisotope scan than by venography. Four histopathological patterns were recognized in the surgically removed adrenal glands, but no correlation between these patterns and clinical behavior or postoperative course was found.     

Editorial: Opportunistic infections due to Aspergillus

Changes in plasma thyroxine (T4) concentrations were followed in 27 fetal sheep after surgical implantation of catheters. Fourteen days were required before stable concentrations of T4 were achieved, whether surgery was performed between 90 and 96 days or 109 and 120 days gestation. Twenty-three fetuses were followed to birth, and during the last four days the T4 concentrations showed no change in 11 fetuses and a significant decrease in the other 12. Birth occurred between 142 and 157 days gestation in both groups. There was a significant rise in T4 concentration during labour in all 23 fetuses. There were large differences among the plasma T4 concentrations of individual ewes which were not related to ambient temperature.     

Intraoral reconstruction in head and neck cancer surgery

The effect of prostaglandins (PGs) on the hepatic biotransformation of hexobarbital (Hechi) and p-chloro-N-methylaniline (PCMA) was determined in male rats. PCMA metabolism in slices was decreased by all PGs (PGA1, PGB1, PGE1, PGE2, PGF1alpha, PGF2alpha), ranging in concentration from 1 mu M to 1 mM. PGA1, at 1 mM, produced the greatest degree of inhibition, 39%. PG addition to microsomes, however, failed to alter PCMA metabolism. In contrast to PCMA biotransformation, Hechi metabolism was increased by all PGs in slices but not in liver subfractions. PGs of the E and F series were the most potent, producing a two-fold increase in Hechi metabolism at 1 mM after a 20 min preincubation. The increased effect was observed as early as 10 min and lasted for 4 hr. The relationship of PG metabolism and binding to cytochrome P-450 is presented as a possible mechanism to account for the opposite effects on Hechi and PCMA, type I and II substrates respectively, metabolism.     

The effect of paraben preservatives on albumin binding of bilirubin

The effect of sodium taurocholate in stepwise increasing infusion rates, 0.3 to 9.6 mumoles per min per kg, on the biliary excretion rate of iodipamide was investigated in 6 dogs (10 experiments) with complete bile diversion under general anesthesia. Iodipamide was administered intravenously with an initial priming dose of 33 mumoles per kg followed by a constant infusion of 1.3 mumoles per min per kg. Although the bile flow continuously increased with an increasing taurocholate dose, the iodipamide excretion rate reached a plateau with a 0.6 mumoles per min per kg of taurcholate infusion, which was 20% higher than with the lowest taurocholate dose. With a taurocholate dose over 2.4 mumoles per min per kg, a significant decrease in the iodipamide rate was found, amounting to 22% of its maximum value with the largest taurocholate dose. The bile iodipamide concentration was already at its maximum with the lowest taurocholate dose, and it decreased with an increasing taurocholate dose. Since the bile iodipamide concentration is probably the most important determinant in clinical cholangiography, low bile salt plasma levels should result in the best radiographic visualization of the biliary tree.     

Serial measurement of arterial plasma progesterone levels throughout gestation and parturition in individual rats

Daily blood samples were taken from 6, chronically cannulated, fully conscious rats to measure plasma progesterone levels throughout gestation. Progesterone levels in individual rats fluctuated by up to 28 ng/ml per day, but tended to be consistently higher or lower than the group mean. The accuracy of predicting progesterone levels in individual rats from previous values was examined. Progesterone levels on day 7 of gestation were negatively correlated with foetal weights near term. There was little indication that high progesterone levels at any stage of gestation lead to increased foetal or placental weights. Progesterone levels on day 17 were positively correlated with the number of corpura lutea but there was little relationship between progesterone and either the number or total mass of the placentas. Serial blood samples taken from a second group of 6 rats at 2 hourly intervals showed that the time between the major fall in progesterone levels to below 12 ng/ml and the onset of parturition was relatively constant (varying by only 8 h) despite a 29 h range in the total length of gestation.     

Prostaglandin F and progesterone secretion by porcine endometrium and corpus luteum in vitro

Slices of porcine endometrium and corpus luteum tissue obtained from mature sows throughout the luteal phase of the oestrous cycle were incubated in culture medium which was analysed at regular intervals over a period of 8 hours for prostaglandin F and progesterone. Prostaglandin F secretion was greatest by endometrium obtained during the mid III to late I luteal stage of the cycle and the increased levels secreted by this tissue were paralleled by high levels of secretion from corpus luteum tissue. The addition of indomethacin (10 mug/ml) to the culture medium completely abolished prostaglandin F secretion by both endometrium and luteal tissue indicating that the high levels of the prostaglandin were due to synthesis. Progesterone secretion by the corpus luteum was maximal from early luteal tissue and had declined to considerably lower levels by late stage tissue when prostaglandin secretion was greatest. The possible physiological significance of luteal prostaglandin F secretion is discussed.     

Effect of cholesterol and cholestyramine feeding and of fasting on sterol synthesis in the liver, lleum, and lung of the guinea pig

The effects of feeding diest containing either cholesterol (0.24% w/w) or cholestyramine (2.5% w/w) and of fasting on sterol synthesis in the liver, ileum, and lung of both male and female guinea pigs have been studied by measuring the incorporation by tissue slices of 14C-labeled acetate into total digitoninpredipitable sterols. Cholesterol feeding significantly decreased (P less than 0.05) sterol synthesis in the liver, ileum, and lung of the males and in the ileum of females. Cholestyramine feeding stimulated the rate of hepatic sterol synthesis 13-fold but did not significantly affect sterologenesis in the ileum. Sterol synthesis in the lung was significantly increased (P less than 0.05) but to a much lesser extent than in the liver. Fatty acid synthesis in the liver, ileum, and lung was not significantly affected by either cholesterol or cholestyramine feeding. In guinea pigs fasted for 24 hr, sterol synthesis was inhibited in all three tissues, the most pronounced effect occurring in the liver. Only in the lung was fatty acid synthesis significantly decreased (P less than 0.001) by fasting. Cholesterol feeding resulted in increased concentrations of cholesterol in the plasma and liver. Cholestyramine feeding reduced plasma cholesterol concentration by 81% in females and by 64% in males. However, it did not significantly change the tissue cholesterol concentrations. Fasting resulted in a significant increase (P less than 0.05) in plasma cholesterol concentration but did not effect the concentration of cholesterol in the tissues. It was concluded that in the normal guinea pig, the feedback inhibition produced by both cholesterol and also possibly by bile acids suppresses sterol synthesis in the liver to very low rates compared to those in the small intestine, where sterologenesis is not only less sensitive to the cholesterol negative feedback system than that in the liver, but also is not subject to regulation by the bile acid negative feedback system.     

Increasing polyunsaturation of milk fats by feeding formaldehyde protected sunflower-soybean supplement

A practical means of protecting fats of a feed concentrate containing high polyunsaturated fatty acids is described. A ground mixture of 30% soybeans and 70% sunflower seeds was treated with 1% formaldehyde to protect the unsaturated lipids from microbial hydrogenation in the rumen. This was fed as a supplement to two Holstein cows in amounts that were doubled weekly. These ranged from 524 to 8384 g/day and provided successively increasing intakes of 100, 200, 400, 800, and 1600 g of linoleic acid daily. Percent milk fat increased by more than one, and linoleic acid (C18:2) of milk fat increased from 2.5 to 20% with compensatory declines in myristic (C14:0) and palmitic (C16:0) acids. Cholesterol and vitamin E of plasma both doubled at the highest supplementation. Milk yield, solids-not-fat, protein and milk cholesterol were unaltered. Fat in feces doubled from about 3 to 6%. Daily linoleic acid content of feces increased from 25 g to 120 g, indicating a dietary loss of 7 to 10% of this polyunsaturated acid. These cheaper feed ingredients elevated the polyunsaturated fats in milk as effectively as the expensive purified casein and safflower oil supplements in previous experiments.     

Acute reductions in serum testosterone levels by narcotics in the male rat: stereospecificity, blockade by naloxone and tolerance

The effects of a single injection of morphine (20 mg/kg) on serum testosterone levels were examined in the male rat. Within 2 hours after the morphine injection, testosterone levels were significantly lower than control levels. The decline in testosterone levels reached a maximum 4 hours after the administration of morphine, at which time testosterone levels were reduced by more than 85% with respect to controls. The ability of a large number of narcotics to depress serum testosterone levels, 4 hours after their administration, was also examined. All narcotics depressed testosterone levels significantly and their potency relative to morphine was comparable to that observed in several other preparations, such as the guinea-pig ileum and mouse vas deferens. The testosterone-depleting effects of the narcotics appear to represent specific narcotic effects since the (-)-isomers of the narcotics were considerably more potent than the (+)-isomers, naloxone competitively inhibited the effects of morphine on testosterone levels and tolerance developed to the testosterone-depleting effects of these drugs. Acute treatment with morphine also lowered serum luteinizing hormone levels, and this reduction preceded the fall in testosterone levels by 1 to 2 hours.